title: Randomized controlled trial of the CGRP receptor antagonist MK-3207 in the acute treatment of migraine.
abstract: BACKGROUND
  This study evaluated the CGRP receptor antagonist MK-3207 for acute treatment of migraine.
  
  
  METHODS
  Multicenter, double-blind, randomized, placebo-controlled, parallel-group, two-stage adaptive study with two interim efficacy analyses to facilitate optimal dose selection. Migraine patients were initially randomized to MK-3207 2.5, 5, 10, 20, 50 and 100 mg or placebo to treat a moderate/severe migraine. One or more doses were to be discontinued based on the first interim analysis and a lower or higher dose could be added based on the second interim analysis. The primary endpoint was two-hour pain freedom.
  
  
  RESULTS
  A total of 547 patients took study medication. After the first interim analysis, the two lowest MK-3207 doses (2.5, 5 mg) were identified as showing insufficient efficacy. Per the pre-specified adaptive design decision rule, only the 2.5-mg group was discontinued and the five highest doses (5, 10, 20, 50, 100 mg) were continued into the second stage. After the second interim efficacy analysis, a 200 mg dose was added due to insufficient efficacy at the top three (20, 50, 100 mg) doses. A positive dose-response trend was demonstrated when data were combined across all MK-3207 doses for two-hour pain freedom (p < .001). The pairwise difference versus placebo for two-hour pain freedom was significant for 200 mg (p < .001) and nominally significant for 100 mg and 10 mg (p < .05). The incidence of adverse events appeared comparable between active treatment groups and placebo, and did not appear to increase with increasing dose.
  
  
  CONCLUSIONS
  MK-3207 was effective and generally well tolerated in the acute treatment of migraine.
authors.affiliation: Merck & Co. Inc., North Wales, PA 19454-1099, USA. david_hewitt@merck.com
authors.forename: David J
authors.initials: DJ
authors.lastname: Hewitt
authors.forename: Sheena K
authors.initials: SK
authors.lastname: Aurora
authors.forename: David W
authors.initials: DW
authors.lastname: Dodick
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Goadsby
authors.forename: Yang Joy
authors.initials: YJ
authors.lastname: Ge
authors.forename: Robert
authors.initials: R
authors.lastname: Bachman
authors.forename: Donna
authors.initials: D
authors.lastname: Taraborelli
authors.forename: Xiaoyin
authors.initials: X
authors.lastname: Fan
authors.forename: Christopher
authors.initials: C
authors.lastname: Assaid
authors.forename: Christopher
authors.initials: C
authors.lastname: Lines
authors.forename: Tony W
authors.initials: TW
authors.lastname: Ho
mesh_terms: D000208:Acute Disease; D000328:Adult; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage* / Q000009:adverse effects; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders / Q000188:drug therapy*; D015990:Placebo Effect; D012720:Severity of Illness Index; D013141:Spiro Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: C548781:2-(8-(3,5-difluorophenyl)-10-oxo-6,9-diazaspiro(4.5)dec-9-yl)-N-(2'-oxo-1,1',2',3-tetrahydrospiro(indene-2,3'-pyrrolo(2,3-b)pyridin)-5-yl)acetamide; D019086:Bridged Bicyclo Compounds, Heterocyclic; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D013141:Spiro Compounds